Zalsupindole

Zalsupindole
Clinical data
Other namesDLX-001; DLX-1; DLX001; DLX1; AAZ-A-154; AAZ; (R)-5-Methoxy-N,N-dimethyl-α-methylisotryptamine; (R)-5-MeO-α-methyl-isoDMT; (R)-5-MeO-N,N-dimethyl-isoAMT
Drug classNon-hallucinogenic serotonin 5-HT2A receptor agonist; Psychoplastogen
Identifiers
IUPAC name
  • (2R)-1-(5-methoxy-1H-indol-1-yl)-N,N-dimethylpropan-2-amine
CAS Number
PubChem CID
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC14H20N2O
Molar mass232.327 g·mol−1
3D model (JSmol)
SMILES
  • CN(C)[C@H](C)Cn1ccc2cc(ccc21)OC
InChI
  • InChI=1S/C14H20N2O/c1-11(15(2)3)10-16-8-7-12-9-13(17-4)5-6-14(12)16/h5-9,11H,10H2,1-4H3/t11-/m1/s1
  • Key:KHEUWLQKCXGVEL-LLVKDONJSA-N

Zalsupindole,[1] also known by its developmental code names DLX-001 and AAZ-A-154 and as (R)-5-methoxy-N,N-dimethyl-α-methylisotryptamine, is a novel isotryptamine derivative which acts as a serotonin 5-HT2A receptor agonist discovered and synthesized by the lab of Professor David E. Olson at the University of California, Davis.[2][3][4][5] It is being developed for the treatment of major depressive disorder and other central nervous system disorders.[2][3]

Animal studies suggest that it produces antidepressant effects without the psychedelic action typical of drugs from this class.[6][7][4][5] In tests, zalsupindole had antidepressant-like effects in mice without causing the head-twitch response linked to hallucinogenic effects.[8][4][5] Due to the rapidly-induced and enduring neuroplasticity, zalsupindole is a member of the class of compounds known as non-hallucinogenic psychoplastogens.[9][4][5] A phase 1 dose-ranging clinical trial confirmed that zalsupindole is non-hallucinogenic in humans across a dose range of 2 to 360 mg.[10]

The drug is selective for the serotonin 5-HT2 receptors.[11] It is an antagonist of the serotonin 5-HT2B receptor and showed no cardiovascular safety signals in animals.[5] Zalsupindole is orally bioavailable and centrally penetrant in animals.[5]

Zalsupindole is a member of the isotryptamine group of compounds.[12][13] It is a combined derivative of isoDMT, 5-MeO-isoDMT, and isoAMT.[12][13] Another related compound is 6-MeO-isoDMT.[12] Zalsupindole is a close isotryptamine analogue of α,N,N,O-tetramethylserotonin (α,N,N,O-TMS).[13]

Zalsupindole, as well as related compounds, are licensed by Delix Therapeutics and are being developed as potential medicines for neuropsychiatric disorders.[9][2][3] As of December 2023, zalsupindole is in phase 1 clinical trials for major depressive disorder and other central disorders.[2][3]

See also

References

  1. ↑ https://iris.who.int/bitstream/handle/10665/380497/9789240107038-eng.pdf "zalsupindolum zalsupindole (2R)-1-(5-methoxy-1H-indol-1-yl)-N,N-dimethylpropan-2-amine antidepressant"
  2. 1 2 3 4 "DLX 1". AdisInsight. 11 December 2023. Retrieved 2 November 2024.
  3. 1 2 3 4 "Delving into the Latest Updates on DLX-001 with Synapse". Synapse. 1 November 2024. Retrieved 2 November 2024.
  4. 1 2 3 4 Rasmussen K, Chytil M, Agrawal R, Leach P, Gillie D, Mungenast A, et al. (2024). "14. Preclinical Pharmacology of DLX-001, a Novel Non-Hallucinogenic Neuroplastogen With the Potential for Treating Neuropsychiatric Diseases". Biological Psychiatry. 95 (10). Elsevier BV: S80. doi:10.1016/j.biopsych.2024.02.192. ISSN 0006-3223.
  5. 1 2 3 4 5 6 Rasmussen K, Engel S, Chytil M, Koenig A, Meyer R, Rus M, et al. (December 2023). "ACNP 62nd Annual Meeting: Poster Abstracts P251 - P500: P361. Preclinical Pharmacology of DLX-001, a Novel Non-Hallucinogenic Neuroplastogen With the Potential for Treating Neuropsychiatric Diseases". Neuropsychopharmacology. 48 (Suppl 1): 211–354 (274–275). doi:10.1038/s41386-023-01756-4. PMC 10729596. PMID 38040810.
  6. ↑ Dong C, Ly C, Dunlap LE, Vargas MV, Sun J, Hwang IW, et al. (May 2021). "Psychedelic-inspired drug discovery using an engineered biosensor". Cell. 184 (10): 2779–2792.e18. doi:10.1016/j.cell.2021.03.043. PMC 8122087. PMID 33915107.
  7. ↑ WO 2020176597, Olson DE, Dunlap L, Wagner FF, "N-substituted indoles and other heterocycles for treating brain disorders", published 3 September 2020, assigned to The Regents of the University of California
  8. ↑ Cross R (2021-09-27). "Delix raises $70 million to synthesize psychedelic-inspired drugs". cen.acs.org. Archived from the original on 2021-09-27. Retrieved 2022-01-14.
  9. 1 2 "Can we take the high out of psychedelics?". Wired UK. ISSN 1357-0978. Retrieved 2022-07-07.
  10. ↑ Koenig A, van der Aa L, Pelletier N, Patat A, Viardot G, Olson D, et al. (2024). "ACNP 63rd Annual Meeting: Poster Abstracts P1-P304: P163. Phase I Results for DLX-001, a Novel Neuroplastogen Under Development for the Treatment of Major Depressive Disorder" (PDF). Neuropsychopharmacology. 49 (S1): 65–235 (157–158). doi:10.1038/s41386-024-02011-0. ISSN 0893-133X. PMC 11627186. PMID 39643633. Retrieved 31 January 2025.
  11. ↑ Dunlap LE (2022). Development of Non-Hallucinogenic Psychoplastogens (Thesis). University of California, Davis. Retrieved 18 November 2024.
  12. 1 2 3 Duan W, Cao D, Wang S, Cheng J (January 2024). "Serotonin 2A Receptor (5-HT2AR) Agonists: Psychedelics and Non-Hallucinogenic Analogues as Emerging Antidepressants". Chem Rev. 124 (1): 124–163. doi:10.1021/acs.chemrev.3c00375. PMID 38033123.
  13. 1 2 3 "(2R)-1-(5-Methoxyindol-1-yl)-N,N-dimethylpropan-2-amine". PubChem. Retrieved 27 November 2024.


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